To demonstrate the technical viability of a medical device for accomplishing the selective immunodepletion of HIV virus and HIV antigens from the plasma of HIV infected patients.
The medical device consists of a specialized immunoabsorption unit coupled with a standard plasmapheresis apparatus. This type of ex^vivo treatment will not deplete HIV infected cells, but only free HIV virions and HIV antigens/immunocomplexes, therefore clinical benefits are expected only by using the treatment on a regular basis and in combination with other standard HIV therapies. Economical calculation of the cost of treatment session will be performed.
The immunoabsorption unit consists of a closed filter system bearing one or more ligands specific for the HIV envelope or for immune complexes, both of which are abundant in HIV infected patients and which contribute to pathogenesis. The immunoabsorption unit will contain recombinant CD4 (CD4 is the natural receptor for HIV) and will deplete both HIV virions and HIV envelope antigens. Another type of immunoabsorption unit produced will contain anti-envelope monoclonai antibodies which, similarly to CD4, directly bind both soluble and virionic envelope antigens.
Other ligands will be used as alternative to CD4 and anti-gp120 antibodies. These ligands will be tested in parallel outside of the contract and will be used for manufacturing the immunoabsorption units only if the testing will demonstrate in vitro efficacy. These alternative ligands are anti-HLA antibodies, which recognize virionic HLA moiecules, complement factor C1 q which has a high affinity for polymeric immunoglobulins like those present in antigen/antibody complexes, GNA lectin which has been recently shown to bind with very high affinity HIV gp120.
The project is divided into two distinct phases: during the first phase specifications of optimal ligand characteristics for the immunoabsorption unit, and manufacturing and quality control protocols will be set. At the end of the first phase three lots of clinical grade immunoabsorption units will be ready to be tested in patients. The second phase will be a phase 1 clinical trial (safety and determination of treatment frequency) on a limited number of patients. The number of patients enrolled will depend on the types of immunoabsorption units available at the end of the first phase (i.e. CD4, anti-gp120, and other alternative ligands).
Funding SchemeCSC - Cost-sharing contracts
75013 Paris/ile De France
105 21 Stockholm
SW17 ORE Tooting London